Mother May I? Managing Mental Illness During Pregnancy: Focus on Antidepressants

Transcription

1 Handout for the Neuroscience Education Institute (NEI) online activity: Mother May I? Managing Mental Illness During Pregnancy: Focus on Antidepressants

2 Learning Objectives Evaluate the potential risks of using antidepressants during pregnancy and postpartum Compare the risk benefit analyses of specific antidepressants for the developing fetus and the breastfeeding infant Identify risk factors for the emergence of depressive symptoms during pregnancy and postpartum

3 Pretest Question 1 The labels for antidepressants (SSRIs in particular) include several warning statements about possible adverse effects of use during pregnancy. Which of the following has the most evidence suggesting an increased risk with antidepressant use during pregnancy? A. First trimester cardiac malformations B. Persistent pulmonary hypertension of the newborn (PPHN) C. Postnatal adaptation syndrome (PNAS) D. Long-term neurodevelopmental abnormalities

4 Major Depression During Pregnancy and Postpartum 20% 18% 16% 14% 12% 10% 8% 6% 4% 2% 0% Period Prevalence Conception to birth Birth to 3 months postpartum Incidence Gaynes N et al. Evidence Report/Technology Assessment No AHRQ Publication No 5-E Rockville, MD: Agency for Healthcare Research and Quality; 2005.

5 ANTIDEPRESSANT USE DURING PREGNANCY

6 FDA Use-in-Pregnancy Ratings A B C D X Controlled studies show no risk No evidence of risk in humans Risk cannot be ruled out Positive evidence of risk What They Really Mean Contraindicated A B C D X OK to use I don't know I don't know I don't know Contraindicated # of Psychotropics With Rating A B C D X

7 Antidepressant Use During Pregnancy Has Been Associated With: First Trimester Cardiac defect Minor physical malformation Major physical malformation Miscarriage Yonkers KA et al. Obstet Gynecol 2011;117:961-77; Pedersen LH et al. Pediatrics 2010;125;e600-8; Field. Int J Neurosci 2010;120:163-7.

8 First Trimester 3% of infants in the US are born with a major birth defect Each specific type of major birth defect is rare Risk of congenital heart defects in general population is 0.82 per 1000 births Why might antidepressants increase the risk of some birth defects? Serotonin is important during early embryonic development of the neural tube, branchial arches, and heart Byatt N et al. Acta Psychiatr Scand 2013;127:

9 Paroxetine Warning in FDA Label Epidemiological studies have shown that infants exposed to paroxetine in the first trimester of pregnancy have an increased risk of congenital malformations, particularly cardiovascular malformations

10 Weighing the Evidence for First Trimester Teratogenicity: Studies Increased Risk (# Studies) No Increased Risk (# Studies) bupropion 2 2 citalopram 4 4 duloxetine 1 0 escitalopram 0 4 fluoxetine 4 7 fluvoxamine 0 4 mirtazapine 0 2 paroxetine 8 7 sertraline 3 6 trazodone 0 2 venlafaxine 1 3 Varying methodology across studies. Causality and magnitude of risk unclear. Byatt N et al. Acta Psychiatr Scand 2013;127:94-114; Hoog SL et al. Int J Med Sci 2013;10(4):413-9; Polen KND et al. Birth Defects Res Part A: Clin Mol Teratol 2013;97(1):28-35.

11 Weighing the Evidence for First Trimester Teratogenicity: Meta-analyses # Meta-analyses Finding Increased Risk Major Cardiac # Meta-analyses Finding No Increased Risk Major Cardiac citalopram fluoxetine paroxetine sertraline SSRI (class) Newer AD (class) AD (class) Myles N et al. Aust N Z J Psychiatry 2013;Epub ahead of print; Addis A, Koren G. Psychol Med 2000;30(1):89-94; Bar-Oz B et al. Clin Ther 2007;29(5):918-26; O'Brien L et al. J Obstet Gynaecol Canada 2008;30(8): ; Wurst KE et al. Birth Defects Res Part A: Clin Mol Teratol 2010;88(3):159-70; Einarson TR et al. J Popul Ther Clin Pharmacol 2012;19(2):w334-48; Nikfar S et al. DARU J Pharm Sci 2013;20(1):75; Einarson TR, Einarson A. Pharmacoepidemiol Drug Safety 2005;14:823-7; Grigoriadis S et al. J Clin Psychiatry 2013;74(4):e ; Riggin L et al. J Obstet Gynaecol Canada 2013;35(4):362-9.

12 Increased Risk of Major Malformations With Antidepressants: Summary Paroxetine Increased risk of major and cardiac malformations in several studies Not seen in large database assessments Bupropion Limited data; possible increased risk of congenital heart defects SSRIs Findings are inconsistently observed Other newer antidepressants Very limited data Absolute risk appears small Byatt N et al. Acta Psychiatr Scand 2013;127:

13 Antidepressant Use During Pregnancy Has Been Associated With: Third Trimester Persistent pulmonary hypertension Postnatal adaptation syndrome Preterm birth Low birth weight Small for gestational age Long-term neurodevelopmental effects? Yonkers KA et al. Obstet Gynecol 2011;117:961-77; Gentile S, Galbally M. J Affective Disord 2011;128(1-2):1-9; Pedersen LH et al. Pediatrics 2010;125;e600-8; Field. Int J Neurosci 2010;120:163-7.

14 Persistent Pulmonary Hypertension of the Newborn (PPHN) At birth, the lung replaces the placenta as the primary site of gas change rapid drop in pulmonary vascular resistance and thus an increase in pulmonary blood flow PPHN can occur when this cardiopulmonary transition does not occur (1 2 cases per 1000 births) Presents within 12 hours of birth as cyanosis and mild respiratory distress Can progress to respiratory failure, requiring intubation and mechanical ventilation; fatal in 10 20% of cases Neonatal Inhaled Nitric Oxide Study Group. J Pediatr 2000;136:611-7; Davidson D et al. Pediatrics 1998;101:325-34; Greenough A, Khetriwal B. Paediatr Respir Rev 2005;6:111-6.

15 FDA Class Statement: PPHN Infants exposed to SSRIs in pregnancy may have an increased risk of persistent pulmonary hypertension of the newborn (PPHN); PPHN occurs in 1 2 per 1000 live births in the general population and is associated with substantial neonatal morbidity and mortality Several recent epidemiological studies suggest a positive statistical association between SSRI use in pregnancy and PPHN Other studies do not show a significant statistical association

16 Weighing the Evidence for Increased Risk of PPHN # Studies Showing Increased Risk of Exposure Early Late # Studies Not Showing Increased Risk of Exposure Early Late fluoxetine SSRI antidepressant Varying methodologies. Studies did not assess duration of exposure. Most studies were underpowered. Chambers CD et al. N Engl J Med 1996;335:1010-5; Chambers CD et al. N Engl J Med 2006;354:579-87; Kallen B, Olausson PO. Pharmcoepidemiol Drug Saf 2008;17(8):801-6; Andrade SE et al. Pharmacoepidemiol Drug Safety 2009;18:246-52; Wichman CL et al. Mayo Clin Proc 2009;84:23-7; Wilson KL et al. Am J Perinatol 2011;28:19-24; Reis M, Kallen B. Psychol Med 2010;40: ; Kieler H et al. BMJ 2011;344:d8012.

17 Increased Risk of PPHN With SSRIs: Summary Unclear if SSRIs are linked to an increased risk of PPHN Possible that any risk is indirect via increased risk of preterm birth If there is an increased risk, what does that mean?

18 Variable No AD during pregnancy PPHN and Antidepressants: Understanding the Risk Definite PPHN (N=377) Matched Control (N=836) 357 (94.7%) 799 (95.6%) 1.0 Adjusted Odds Ratio (95% CI) P-value AD before wk 20 6 (1.6%) 26 (3.1%) 0.6 ( ) 0.28 AD after wk (3.7%) 11 (1.3%) 3.2 ( ) No SSRI during pregnancy Study With Highest Relative Risk With AD Use 361 (95.8%) 812 (97.1%) 1.0 SSRI before wk 20 2 (0.5%) 18 (2.2%) 0.3 ( ) 0.08 SSRI after wk (3.7%) 6 (0.7%) 6.1 ( ) Chambers CD et al. N Engl J Med 2006;354:

19 PPHN and Antidepressants: Understanding the Risk Variable Definite PPHN (N=377) Matched Control (N=836) Adjusted Odds Ratio (95% CI) What does the relative risk mean? P-value SSRI after wk (3.7%) 6 (0.7%) 6.1 ( ) Population risk: 1 2 per 1000 Absolute risk w/ SSRI: 6 12 per 1000 In other words: Rate of no PPHN in population: ~99% Rate of no PPHN w/ SSRI: ~99% Chambers CD et al. N Engl J Med 2006;354:

20 Postnatal Adaptation Syndrome (PNAS) 20 30% of infants exposed to SSRIs in late pregnancy exhibit symptoms such as irritability, abnormal crying, tremor, lethargy, hypoactivity, decreased feeding, tachypnea, and respiratory distress Termed PNAS; also called neonatal behavioral syndrome or poor neonatal adaptation syndrome Usually develops within days of birth and resolves within days or weeks Byatt N et al. Acta Psychiatr Scand 2013;127:

21 FDA Class Statement: Postnatal Adaptation Syndrome Neonates exposed to SSRIs or SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding; such complications can arise immediately upon delivery Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying These features are consistent with either a direct toxic effect of SSRIs and SNRIs or possibly a drug discontinuation syndrome

22 Weighing the Evidence for Risk of PNAS # Studies Showing Increased Risk of Exposure Some conflicting evidence Varying methodologies # Studies Not Showing Increased Risk of Exposure 12 4 Overall, data suggest that PNAS can occur in neonates exposed to SSRIs or SNRIs Most often reported after exposure to paroxetine, fluoxetine, or venlafaxine Byatt N et al. Acta Psychiatr Scand 2013;127:

23 PNAS: Why and How It May Occur All SSRIs cross the placenta and thus may increase serotonin in the developing fetus Suggested causes of PNAS Serotonin toxicity (symptoms resemble serotonin syndrome) Discontinuation syndrome (symptoms resemble adult serotonin discontinuation syndrome) Severity and duration of PNAS are affected by: Antidepressant dose, timing, duration of exposure, and pharmacokinetics Genetic predisposition? Sie SD et al. Arch Dis Child: Fetal Neonatal Ed 2012;97:F472-6.

24 Long-term Neurodevelopmental Very limited data Outcomes No studies found detrimental effects on cognitive development Two studies found possible effects on motor development Studies that exist are reassuring but have limitations Most did not follow children through school-age Most did not control for maternal IQ Most did not measure maternal treatment adherence Gentile S, Galbally M. J Affective Disord 2011;128:1-9.

25 FDA Class Statement: AD Discontinuation and Depression Relapse Physicians should also note the results of a prospective longitudinal study of 201 pregnant women with a history of major depression who were either on antidepressants or had received antidepressants less than 12 weeks prior to their last menstrual period and were in remission Women who discontinued antidepressant medication during pregnancy showed a significant increase in relapse of their major depression compared to those women who remained on antidepressant medication throughout pregnancy

26 Time to Depression Relapse for Medication Maintenance vs. Discontinuation 5-fold increased risk of relapse for discontinuation vs. maintenance Cohen LS et al. JAMA 2006;295(5):

27 Time to Depression Relapse for Medication Reintroduction vs. No Reintroduction Cohen LS et al. JAMA 2006;295(5):

28 Risks of Untreated Depression During Pregnancy Miscarriage Inadequate maternal weight gain Poor self-care Substance use Preeclampsia Postpartum depression Cesarean delivery Impaired fetoplacental function Preterm birth Low birth weight Small for gestational age Fetal distress Neonatal care unit admittance Byatt N et al. Acta Psychiatr Scand 2013;127:

29 Risk Benefit Analysis: Depression vs. Antidepressants No randomized controlled trials comparing risk of depression vs. antidepressants Inadequate maternal weight gain Miscarriage Poor maternal self-care Cardiac defect Substance use Preeclampsia Impaired fetoplacental function Fetal distress Cesarean delivery Neonatal care unit admittance Postpartum depression Preterm birth Low birth weight Small for gestational age Long-term neurodevelopmental abnormalities? Major malformation Persistent pulmonary hypertension? Postnatal adaptation syndrome

30 Treated vs. Untreated Depression: Propensity Score Matching Outcome Differences SE-D DE DE Nonexposed Difference P-value Difference P-value C-section <0.001 Birth weight, g <0.001 Gestational Gestational age, wk age, wk: (SE-D) vs <.001 (DE) vs (Nonexposed) <.001 Preterm birth < Birth weight <10 th percentile Length of hospital stay, d Hospital stay >3 d < <0.001 Respiratory distress 1, < Feeding problems Jaundice Convulsions Incidence. 2 For gestational age. 3 Also significant for subgroup born vaginally. SE-D: depressed, treated w/ SSRI. DE: depressed, not treated w/ medication. Oberlander TF et al. Arch Gen Psychiatry 2006;63:

31 Treated vs. Untreated Depression: Propensity Score Matching Outcome Differences, SE-D DE Unmatched Propensity score matched Difference P-value Difference P-value C-section Birth weight, g Gestational age, wk < Preterm birth < Birth weight <10 th percentile Length of hospital stay, d Hospital stay >3 d 0.05 < Respiratory distress 1, < Feeding problems Jaundice Convulsions Incidence. 2 For gestational age. 3 Also significant for subgroup born vaginally. SE-D: depressed, treated w/ SSRI. DE: depressed, not treated w/ medication. Oberlander TF et al. Arch Gen Psychiatry 2006;63:

32 Treated vs. Untreated Depression: Prospective Data Study 1: increased risk of lower gestational age and preterm birth with prenatal antidepressant use but not with untreated depression Natural design; N=90; treated vs. untreated vs. control; comparable levels of depression in both treated and untreated groups Study 2: increased risk of preterm birth for both prenatal antidepressant use and untreated depression Natural design; N=238; treated vs. untreated vs. control; lower depression levels in treated group Suri R et al. Am J Psychiatry 2007;164: ; Wisner KL et al. Am J Psychiatry 2009;166:

33 Why Is it So Hard to Interpret Study Results? Different methodologies, each with limitations Retrospective case-control: recall bias, high nonresponse rate Prospective interview: small sample size Drug registry: unclear if patients actually took the drug as prescribed Untreated disorder as a confounding factor Carries risks as well Severity may be related to medication use Drugs may be used for different disorders Byatt N et al. Acta Psychiatr Scand 2013;127:

34 Antidepressants During Pregnancy: Summary Possible small absolute risk of major malformations Possible small absolute risk of PPHN 20 30% rate of PNAS in exposed infants Unclear long-term neurodevelopmental effects Possible increased risk of lower gestational age (clinical significance?) and preterm birth

35 Preconception Planning for Patients on an Antidepressant: Guidelines Moderate to severe symptoms? No Yes Consider period of stability before attempting to conceive Started antidepressant <6 months ago? No Recurrent episodes of MDD? Yes Consider period of stability before attempting to conceive No Yes Previously responded to psychotherapy? Patient may be eligible for a trial off medication with referral for psychotherapy, unless she wants to continue Yes No Consider continuation unless patient wants to discontinue Yonkers KA et al. Obstet Gynecol 2009;114:

36 Untreated Pregnant Patients With a Current MDE: Guidelines Patient willing to consider pharmacotherapy? No Yes Treated with psychotherapy in the past? Patient may be eligible for psychotherapy alone No Yes Failed to respond to psychotherapy? No Yes Consider treatment with an antidepressant, assuming patient assessment and history do not reveal evidence of bipolar disorder Yonkers KA et al. Obstet Gynecol 2009;114:

37 Pregnant Patients on an Antidepressant: Guidelines Patient considering discontinuing pharmacotherapy? Continue antidepressant; monitor No Yes Treated with psychotherapy in the past? No Does the patient have current moderate to severe symptoms? Yes Failed to respond or relapsed with psychotherapy in the past? No Yes No Yes Previously relapsed after stopping antidepressant? Consider psychotherapy; reevaluate medication need Continue antidepressant; monitor Consider taper; No Yes monitor Yonkers KA et al. Obstet Gynecol 2009;114:

38 FDA Use-in-Pregnancy Categories for Antidepressants (for What They're Worth) B C D maprotiline amitriptyline amoxapine bupropion citalopram clomipramine desipramine desvenlafaxine doxepin duloxetine escitalopram fluoxetine fluvoxamine isocarboxazid milnacipran mirtazapine nefazodone phenelzine protriptyline selegiline sertraline tranylcypromine trazodone trimipramine venlafaxine vilazodone Preferred / Most Data: fluoxetine (not during lactation) sertraline paroxetine citalopram imipramine nortriptyline paroxetine Sie SD et al. Arch Dis Child: Fetal Neonatal Ed 2012;97:F472-6; Byatt N et al. Acta Psychiatr Scand 2013;127:

39 Depression Treatment Guidelines SSRIs are generally considered first-line in pregnancy Strongly consider an antidepressant that the woman is currently responding to or has responded to in the past to avoid unnecessary exposures during pregnancy Use lowest possible dose, but avoid undertreatment (could lead to dual exposure of drug and depression) Maximize non-medication evidence-based treatments Avoid polypharmacy unless it is clearly indicated Tapering antidepressants in the third trimester has not been shown to decrease the incidence of postnatal adaptation syndrome or improve infant outcomes * Byatt N et al. Acta Psychiatr Scand 2013;127:94-114; *Warburton W et al. Acta Psychiatr Scand 2010;121(6):471-9.

40 Shared Decision Making Provide the patient with the information needed to make an informed decision Involve the family (father, grandparents) Ensure proper communication with other care providers Confirm that the patient has a support system

41 If a Patient Chooses to Discontinue Her Antidepressant: General Management Advise to resume antidepressant treatment shortly after delivery in order to mitigate the risk of postpartum depression Advise to report the onset of any depressionrelated symptoms Schedule follow-up appointment Communicate with the OBGYN

42 If a Patient Chooses to Discontinue Her Antidepressant: "Stimulating" Treatments Treatment Evidence in Pregnancy or Postpartum Psychotherapy 1 positive randomized trial with IPT in postpartum depression 1 1 positive open-label trial of partner-assisted IPT in perinatal and postpartum depression 2 Exercise Bright light therapy 1 positive randomized study (N=80) in pregnant women with no history of depression 3 1 positive small open-label trial in perinatal depression 4 1 positive small randomized trial in perinatal depression 5 1 negative small randomized trial in perinatal depression 6 1. O'Hara MW et al. Arch Gen Psychiatry 2000;57: Brandon AR et al. Arch Womens Ment Health 2012;15(6): Robledo-Colonia AF et al. J Physiother 2012;58(1): Oren DA et al. Am J Psychiatry 2002;159: Epperson CN et al. J Clin Psychiatry 2004;65: Wirz-Justice A et al. J Clin Psychiatry 2011;72(7):

43 If a Patient Chooses to Discontinue Her Antidepressant: "Stimulating" Treatments Treatment Evidence in Pregnancy or Postpartum rtms Positive published case reports 1 1 positive small open-label trial 2 ECT Positive published case reports 3-5 Acupuncture 1 positive randomized trial (N=150) in perinatal depression 7 1 small negative trial in postpartum depression 8 1. Richards EM, Payne JL. CNS Spectrums 2013;Epub ahead of print. 2. Kim DR et al. J Womens Health (Larchmont) 2011;20(2): O'Reardon JP et al. J ECT 2011;27:e Anderson EL, Reti M. Psychosom Med 2009;71(2): Gahr M et al. Pharmacopsychiatry 2012;45(2): Bulut M et al. J ECT 2013;29(2):e Manber R et al. Obstet Gynecol 2010;115(3): Chung KE et al. J Affective Disord 2012;142(1-3):

44 If a Patient Chooses to Discontinue Her Antidepressant: Herbal Treatments Treatment Evidence in Pregnancy or Postpartum Omega-3 1 positive small double-blind trial in perinatal depression 1 3 negative double-blind trials (N=118) in perinatal depression 2-4 Folate Thyroid hormone Vitamin D Prospective chart review (N=6809) was negative for perinatal depression but positive for postpartum depression at 21 months 5 Not studied; subset of patients may have abnormal thyroid levels Not studied; low vitamin D levels have been associated with perinatal depression 6 1. Su KP et al. J Clin Psychiatry 2008;69(4): Mozurkewich EL et al. Am J Obstet Gynecol 2013;208(4):313.e Freeman MP et al. J Affective Disord 2008;110(1-2): Rees AM et al. Aust N Z J Psychiatry 2008;42(3): Lewis SJ et al. Eur J Clin Nutr 2012;66(1): Cassidy-Bushrow AE et al. J Womens Health (Larchmont) 2012;21(11):

45 ANTIDEPRESSANT USE POSTPARTUM

46 Risk Factors for Postpartum Depression Previous major depressive episode Untreated depression during pregnancy Life stress Lack of social support Family history of postpartum depression Yonkers KA et al. Obstet Gynecol 2011;117:

47 Risks of Postpartum Depression Disruption of maternal infant bonding Self-harm Harm to infant Difficult temperament Attachment insecurity Cognitive delay Developmental delay Behavioral problems Difficulty with social interaction Byatt N et al. Acta Psychiatr Scand 2013;127:

48 Drug Exposure in Breast Milk Exposure can vary between women and within the same woman at different times Drug characteristics (lipid solubility, dose, metabolism) Genetic influence (enzyme activity of mother/child) Timing of feeding vs. medication ingestion Yonkers KA et al. Obstet Gynecol 2011;117:961-77; Sie SD et al. Arch Dis Child: Fetal Neonatal Ed 2012;97:F472-6.

49 Antidepressants and Lactation Drug (~Descending Order of Available Data) Relative Infant Dose (%)* fluoxetine up to 80 sertraline paroxetine citalopram 3 10 up to 10 fluvoxamine <2 -- venlafaxine 6 9 up to 30 escitalopram 3 6 <4 mirtazapine <1 bupropion 2 -- duloxetine <1 -- desvenlafaxine Relative Infant Plasma Concentration (%)** *Infant dose (mg/kg/d) divided by maternal dose (mg/kg/d). Value <10% is considered negligible. **Infant plasma concentration divided by maternal plasma concentration OR by what is considered a low therapeutic adult concentration. Sie SD et al. Arch Dis Child: Fetal Neonatal Ed 2012;97:F472-6; Chad L et al. Can Fam Physician 2013;59:633-4; Berle JO, Spiqset O. Curr Womens Health Rev 2011;7(1):28-34.

50 Antidepressant Use During Pregnancy L1 (safest) L2 (safer) amitriptyline amoxapine clomipramine desipramine fluvoxamine imipramine nortriptyline paroxetine sertraline trazodone and Lactation L3 (moderately safe) bupropion citalopram escitalopram fluoxetine* maprotiline mirtazapine venlafaxine ACOG Practice Bulletin. Obstet Gynecol 2008;111(4): L4 (possibly hazardous) nefazodone L5 (contraindicated) doxepin *Neonates only; L2 in older infants. Categories were not identified for desvenlafaxine, duloxetine, isocarboxazid, milnacipran, phenelzine, protriptyline, selegiline, tranylcypromine, or trimipramine.

51 Breastfeeding Treatment Guidelines Generally preferred Sertraline and paroxetine Most data Negligible relative infant doses/concentrations Generally not preferred Fluoxetine, venlafaxine, and citalopram Highest infant plasma concentrations (flu, ven) Case reports of possible adverse effects (flu, cit) After 3 6 months of age, the capacity to metabolize drugs is matured, and measurable infant plasma levels are not expected (Metabolic capacity takes longer to mature in preterm infants) Sie SD et al. Arch Dis Child: Fetal Neonatal Ed 2012;97:F472-6; Chad L et al. Can Fam Physician 2013;59:633-4; Berle JO, Spiqset O. Curr Womens Health Rev 2011;7(1):28-34.

52 Breastfeeding Treatment Guidelines (cont.) Generally not necessary to recommend that women needing antidepressants abstain from breastfeeding Although some agents are less preferred, they can be considered in women who took them during pregnancy or have had previous effectiveness with them Often recommended to take the medication immediately after breastfeeding and prior to the infant's sleep time in order to minimize exposure to peak drug concentrations Likely only reduces infant drug intake to a small extent No benefit of "pump and dump" Infants should be monitored for adverse effects, such as sedation, irritability, or change in sleep/feeding pattern Berle JO, Spiqset O. Curr Womens Health Rev 2011;7(1):28-34.

53 If a Patient Does Not Want to Take Medication While Breastfeeding "Breast is best"; however, the risks of untreated postpartum depression may well outweigh the benefits of breastfeeding Can consider nonpharmacological treatment If nonpharmacological treatment is unavailable or considered insufficient, encourage bottle feeding over treatment discontinuation Support the mother in her decision and monitor her carefully

54 Summary Existing data suggest that the benefits of antidepressant treatment during pregnancy and postpartum may outweigh the risks Breastfeeding does not need to be discontinued if antidepressants are used postpartum Whether or not to treat with antidepressants should be a shared decision between a clinician and an informed patient Ultimately, the decision belongs to the patient; support her as an ally and offer alternative treatment suggestions if needed

55 A Quick Word on Antipsychotics Haloperidol is most frequently used Best-studied atypical antipsychotics are olanzapine, risperidone, quetiapine, and clozapine Exposure to antipsychotics during the last gestational week may cause postnatal disorders Habermann F et al. J Clin Psychopharmacol 2013;33: